Butyrate cytoprotection of colonic epithelial cells may be mediated through inhibition of heat shock protein 70

Abstract

Butyrate, normally found in the colon, is used in therapy to reduce epithelial cell damage and mucosal inflammation in conditions like ulcerative colitis and radiation colitis. Heat shock proteins (Hsp), particularly Hsp70, are also known to be important in cellular responses to injury. We hypothesized that butyrate may act to protect epithelial cells through induction of Hsp70. HT29 intestinal epithelial cell monolayers were exposed to two forms of non-lethal stress; heat or chemical in presence or absence of butyrate. Cells were radiolabeled with ³⁵S-methionine and incubated at 37°C for 2 h. Cells were lysed, subjected to 1D SDS-PAGE, followed by autoradiography. In additional studies, the effect of initial exposure to sub-lethal heat on subsequent exposure to lethal heat was examined. Expression of the inducible form of Hsp70 and cell viability was assessed. Non-lethal stress induced Hsp70 expression in HT29 cells and this was inhibited by butyrate, but not by acetate or propionate. This effect of butyrate was seen only at lower concentration. Inhibition of Hsp70 synthesis was accompanied by an increased ability of the cells to tolerate exposure to a second lethal heat stress. Butyrate increased colonic epithelial cell survival in the face of lethal heat stress and significantly reduced Hsp70 expression.